This phase IIa trial compares the safety and effect of temozolomide combined with survivin long peptide vaccine (SurVaxM) to temozolomide alone in patients with neuroendocrine tumors (NET) that has spread from where it first started (primary site) to other places in the body (metastatic) and is growing, spreading or getting worse (progressing). Temozolomide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid and may kill tumor cells and slow down or stop tumor growth. Survivin, a protein, is expressed in 50% of patients that have neuroendocrine tumors and, is associated with poor outcomes. SVN53-67/M57-KLH peptide vaccine (SurVaxM) is a vaccine that has been shown to produce an immune system response against cancer cells that express a survivin and may block the growth of new tumor cells. Giving temozolomide with SurVaxM may kill more tumor cells in patients with progressing metastatic neuroendocrine tumors.
PRIMARY OBJECTIVES: * To determine the clinical efficacy (progression free survival \[PFS\]) of combining temozolomide and SVN53-67/M57-KLH peptide vaccine (SurVaxM) in patients with progressing NECs. * To evaluate the safety and toxicity of the study drug combination (temozolomide + SurVaxM) in patients with progressing NECs. SECONDARY OBJECTIVES: I. To assess clinical benefit (including complete response, partial response and stable disease as defined by Response Evaluation Criteria in Solid Tumors \[RECIST\] version \[v\]1.1) at 3 months, 6 months, 9 months, and 12 months from study entry. II. To assess anti-survivin IgG titer response. EXPLORATORY OBJECTIVES: I. To explore immune markers associated with clinical responses to SurVaxM in peripheral blood of NETs patients. II. To assess the methylguanine methyltransferase (MGMT) status of all patients and correlate with response. III. To assess the tumor growth rate (TGR) on radiographic imaging prior to study enrollment and while on study. OUTLINE: Patients receive temozolomide orally (PO) once daily (QD) on days 1-5. Treatment repeats every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity and can be continued at investigators discretion at end of treatment. Patients also receive SurVaxM with incomplete Freund's adjuvant (montanide ISA-51) subcutaneously (SC) and sargramostim SC once every 2 weeks for 4 doses. Patients with clinical benefit after 4 doses of SurVaxM and remain free of tumor progression and unacceptable toxicity may receive 3 additional doses on weeks 24, 36, and 48. Additionally, patients undergo blood sample collection, computed tomography (CT) scans or magnetic resonance imaging (MRI) scans throughout study. After completion of study treatment, patients are followed up at 30 days.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
60
Undergo blood sample collection
Undergo CT scan
Given SC
Undergo MRI
Given SC
Given SC
Given PO
Roswell Park Cancer Institute
Buffalo, New York, United States
Progression free survival (PFS)
Summarized using frequencies and relative frequencies.
Time frame: At 6 months
Incidence of adverse events
Defined using National Cancer Institute (NCI) Common Terminology Criteria for Adverse events (CTCAE) version (v) 5.0. Adverse events will be summarized by attribution and grade using frequencies and relative frequencies.
Time frame: Up to 1 year
Response
Assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. Response will be summarized by time-point using frequencies and relative frequencies. Clinical benefit (best response of complete response \[CR\], partial response \[PR\] or stable disease \[SD\]) will be estimated and summarized using frequencies and relative frequencies, with a 95% confidence interval obtained for the clinical benefit rate.
Time frame: At 3, 6, 9 and 12 months from study entry
Overall survival (OS)
OS will be summarized using standard Kaplan-Meier methods, where the median will be estimated with a 95% confidence interval.
Time frame: At the time from treatment initiation until death due to any cause up to 1 year
Time to progression (TTP)
Defined using RECIST v1.1. TTP will be summarized using standard Kaplan-Meier methods, where the median will be estimated with a 95% confidence interval.
Time frame: At the time from treatment initiation until disease progression, death or last follow up up to 1 year
Titer response
Defined as anti-survivin IgG titers \> 30,000 and will be summarized using frequencies and relative frequencies.
Time frame: Up to 1 year
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